Schizophrenia is a major public health problem that affects 1% of the general population and has devastating effects on the psychological an financial resources of the patient, family, and larger community. Unfortunately there is still no clear understanding of the pathology although recent research has made it increasingly clear that biological factors may play an important role. One promising area of research has focused on the detection of abnormalities in the brains of patients afflicted with schizophrenia. Here, both post-mortem and recent magnetic resonance (MR) structural imaging studies suggest that temporal lobe and temporal lobe limbic system abnormalities, especially pronounced on the left, may be implicated in the pathophysiology of schizophrenia. The goal of the current proposal is to define and to localize further brain abnormalities in the temporal lobe in patients afflicted with schizophrenia. We plan to employ image processing techniques, originally developed for the analysis of multichannel remote sensing data (i.e., satellites), to analyze high spatial resolution MR scans (1.5-mm and 2-mm slices) from 75 male, right-handed, chronic schizophrenics and 75 normal control subjects matched for age, sex, handedness, and parental social class. The application of these newly developed image processing techniques to the investigation of schizophrenia is particularly promising because these techniques not only exploit more fully information contained in MR scans, but they also offer more precise and accurate measurements, factors important to schizophrenia where brain abnormalities are often more subtle, and harder to detect, than for other pathophysiological disorders, and where, consequently, precise and accurate measurements become that much more essential. These techniques will be used to make volumetric measurements of: 1) whole brain for gray matter, white matter and CSF; 2) temporal lobe (gray and white matter); 3) amygdala-hippocampal complex, 2) parahippocampal gyrus, 4) superior temporal gyrus; 5) cingulate gyrus; and 6) prefrontal lobe gyri. In addition, an analysis of the gyral pattern in the cortical gray matter surface of the temporal lobes will be completed. We predict that schizophrenics, compared to normal controls, will show reductions in volume in temporal lobe limbic system structures (amygdala- hippocampal formation and parahippocampal gyrus), and in superior temporal gyrus. We further predict that these abnormalities will be more pronounced on the left, and will be correlated with each other, thus indicating damage to an interconnected neural network, as well as correlated with positive but not negative systems. We expect that these abnormalities will also be visible in 3D reconstructions of cortical gray matter where schizophrenics will show an abnormal gyral pattern on the left. We also expect cingulate gyrus volume to be correlated with tissue reductions in neuroanatomically linked regions in the temporal lobe. By applying these new techniques to assess heretofore unmeasurable differences between the brains of normal control subjects and patients afflicted with schizophrenia, we hope to understand better the pathophysiology of this disorder.